This proposal seeks funds for the support of a continuing project that has as its ultimate goals the following: (1) to attain a comprehensive understanding of the complex factors that play a role in adverse reactions resulting from utilization of x-ray contrast-media; (2) to undertake the synthesis of new and better media based on an understanding and, hence, avoidance of those factors that, at the molecular level, tend to play a role in the production of adverse reactions. As in the past, it is proposed that this program will be carried out by a group of individuals with broad experience in the field of contrast material research. Continuing studies will explore (1) further elaboration of the chemical basis for contrast-tissue interactions, (2) the subcellular basis for reactions and for metabolic handling of the contrast media, (3) the response of individual cells and of organs to perfusion with high concentrations of the contrast media, and (4) the formulation of new media based on knowledge acquired by this group and by others. The chemical studies will revolve largely around the acquisition of further detail regarding contrast protein interactions, and particularly, the effects of contrast media on enzyme kinetics and on membrane permeability. At the organ level, particular attention will be paid to the pathogenesis of adverse effects of contrast material perfusion in the brain, heart and kidney. In terms of tissue distributions particular attention will be paid to the liver and the mechanisms within the liver that govern the transfer of contrast media to the bile. Finally, increasing attention will be paid to the synthesis of new media and the development of better in vitro and in vivo screening tests for these.